Many cases of acute gastroenteritis in Man and domestic animals are not associated with well-recognized bacterial or viral pathogens. Several lines of investigation have incriminated members of the "normal" intestinal fora, particularly Escherichia coli, as the culprits. Our proposed research attempts to define the capacity of these microorganisms to cause disease and to define ways for the development of preventive measures. Our research has focused upon the genetic basis for enterotoxin production and specific adhesive propeties of E. coli strains isolated from cases of diarrheal disease. The capacity to elaborate enterotoxin as well as to adhere to small bowel epithelium has been found to be plasmid mediated. We have cloned the structural genes for E. coli heat-stable and heat-labile enterotoxin as well as one gene which specifies adherence to swine small bowel epithelium onto small plasmid cloning vehicles. These cloned determinants are currently being employed for the study on in vitro toxin biosynthesis. In addition, specific deletions of the toxin structural gene have been isolated so that an immunologically active but non-toxic polypeptide is now synthesized. BIBLIOGRAPHIC REFERENCES: So, M., R. Gill and S. Falkow. 1976. The generation of a Co1E1 Apr cloning vehicle which allows detection of inserted DNA. Molec. Gen. Genetics. 142:239. So, M., H.W. Boyer, M. Betlach, and S. Falkow. 1976. Molecular cloning of an Escherichia coli plasmid determinant that encodes for the production of heat-stable enterotoxin, J. Bacteriol. 128:463.